Chronic tophaceous gout is the natural evolution of untreated gouty arthritis and is characterized by the deposition of solid monosodium urate crystal aggregated in a variety of tissue including joints, bursae and tendons. Tophaceous gout is well-known to cause bone erosions and is characterized by enhanced osteoclasts development. Peripheral blood mononuclear cells (PBMCs) from patients with severe erosive gout showed the preferential ability to transform into osteoclast-like cells following stimulation with receptor activator of NF-κB ligand (RANKL). Crossostephium chinense (CC) is a traditional Chinese medicinal plant used to treat arthralgia and rheumatism. CC had been proved to have antioxidant, antiproliferative and hepatoprotective activities. This study is aimed to investigate the effects of CC extract (CCE) on the formation of RANKL-activating osteoclasts from RAW264.7 macrophage cells and from PBMCs in patients with tophaceous gout. The study was approved by the Human Research Ethics Committee (No. EMRP-101-059). Written informed consents were obtained from gouty patients before enrollment. CCE significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts in a dose-dependent manner. CCE suppressed RANKL-stimulated osteoclast differentiation in RAW264.7 cells via down-regulating activation of TRAF6, NF-κB and MAPKs including ERK, JNK, p38 and the expression of NFATc1 and MMP-9. Additionally, CCE decreased the phosphorylation of osteoclasts survival-related signaling molecules, including TRAF6, NF-κB, ERK, JNK, p38, NFATc1 and MMP-9. Furthermore, CCE inhibited pits formation on bone slices in a dose-dependent manner that indicated the ability to inhibit the bone resorptive activity of mature osteoclasts. On the other hand, CCE was capable of suppressing RANKL-mediated differentiation and formation of TRAP-positive multinucleated osteoclasts transformed from PBMCs. CCE also decreased bone resorptive activity of mature osteoclasts derived from PBMCs. Taken together, these results demonstrate that CCE have potential in treating gouty erosions through inhibiting differentiation, formation and bone resorptive ability of osteoclasts.
17 May 2014 - 20 May 2014